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By Dr. Priyom Bose, Ph.D. Reviewed by Danielle Ellis, B.Sc.

What happens after HIV infection?
Evolution of HIV diagnostic assays
Conclusions
References
Further reading

Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV) that attacks the body’s immune system, making it vulnerable to all infections. One of the major concerns of the early AIDS epidemic that began in 1981 was the lack of proper diagnostic measures to identify infected individuals.1 Since the development of the first HIV diagnostic assay in 1985, scientists have continued to improve diagnostic accuracy, detection speed, and cost.

Image Credit: Hanna Karpiak/Shutterstock.com What happens after HIV infection?

The immune system produces antibodies after encountering harmful foreign substances or antigens. HIV infects the vital cells associated with immunity, such as macrophages, helper T cells, and dendritic cells, and disrupts their function. The three important HIV antigens are p24, gp 41, and gp 120.2

HIV is a slow-replicating retrovirus that is transmitted through sexual intercourse, sharing an infected needle, or by blood transfer.3 After HIV infection, the viral load cannot be measured immediately due to low plasma load. Typically, the viral RNA can be measured within 10 to 12 days after infection.4

Antibodies to p24 and gp 41 are the first serological markers used to detect HIV infection. IgG antibodies appear approximately three weeks after infection. In the majority of HIV-infected individuals, HIV antibodies appear to circulate within 1 to 2 months of the infection. However, in a few cases, it may take up to six months to appear at a detectable level.5 Evolution of HIV diagnostic assays

Over the years, scientists have developed many immunoassays and nucleic acid amplification tests (NAATs) to accurately and high-throughput HIV diagnosis. These tests are broadly divided into two categories, namely, screening and confirmatory tests. Typically, HIV tests are performed on blood, oral fluids, or urine samples.6

HIV screening is performed by various immunoassays that focus on detecting IgG antibodies against HIV-1 antigens in the serum. Techniques such as Western blot, line immunoassay (LIA), and recombinant immunoblot are used as confirmatory tests.7 Some of the important HIV diagnostic assays are discussed below: Serological testing for HIV

In the mid-1980s, simple serological tests for HIV antibodies were developed based on culture-derived viral antigen preparation.7 These tests enabled HIV diagnosis and assessed blood and blood product supplies. Since the early assays, various serological assays have been developed that aided simple/rapid testing, high-throughput screening, confirmatory tests, incidence determination, and epidemiological surveillance. Since its first development, five generations of enzyme immunoassays (EIAs) have emerged based on varied antigen preparations and detection chemistries.8

First-generation assays: The first-generation EIAs detect IgG antibodies from antigens derived from whole viral lysates of HIV-positive cultures. Since crude antigen lysate contains impurities, this method exhibited reduced specificity and high false positivity. In contrast, immunofluorescence assays or Western blotting (WB) have shown higher specificity and lower false positivity.

Second-generation assays: Second-generation assays involve the use of recombinant proteins or synthetic peptides derived from the immunodominant regions (IDR) of HIV-1 proteins and gp36 of HIV-2, which increases sensitivity and decreases false positivity.

Third-generation assays: Third-generation assays, including the Genetic Systems HIV-1/HIV-2 Plus O EIA, use a variety of antigens to detect HIV-1 and -2 antibodies in the serum. A major advantage of third-generation sandwich format assays is their ability to detect HIV-1 IgM antibodies early, enabling quicker HIV diagnosis.

Fourth-generation assays: The fourth-generation EIAs, including the Abbott Architect HIV Ag/Ab Combo assay, utilize fully automated chemiluminescent microparticle technology that can instantaneously identify antibodies to HIV-1 and HIV-2 and HIV-1 p24 antigen. This technique has further allowed early HIV diagnosis. Other advantages of fourth-generation high-throughput assays are their capacity to perform more than 150 tests per hour and their ability to test specimens immediately upon arrival and generate results within 30 minutes.  These assays are suitable for facilities, such as blood banks, that handle high volumes of blood samples.

Fifth-generation assays: Fifth-generation assays, such as the Bio-Rad BioPlex 2200 HIV Ag-Ab assay, use magnetic beads coated with p24 monoclonal antibodies and epitopes specific for HIV-1 and HIV-2. This type of assay has a major advantage in  that it can confirm HIV infection in a single test. Interested in Assay Kits? Explore Equipment Here

Despite the advancements in EIA assays, the challenges associated with the generation of false positive results persist. Therefore, EIA-reactive specimen is typically retested with supplemental tests, such as Western Blot. Rapid diagnostic tests Related StoriesSweden exceeds UNAIDS HIV goals but faces new challengesNutrition's pivotal role in combating tuberculosis: addressing N-AIDS for better outcomes

The first HIV rapid test was available in the early 1990s. It determined an individual's serostatus before surgery, maternal labor/delivery, and organ transplant. Rapid diagnostics is based on immunochromatographic technology that uses blood from finger pricks to assess HIV status. 9 This test can provide results in less than 30 minutes and can be used in point-of-care (POC) settings. Since this test presents both false positive and negative results, it is essential to confirm the findings with laboratory-based HIV assays.

The main advantage of this technique is that any non-laboratory staff can perform it in a primary health care center. Even though decentralization of HIV diagnostic services has increased HIV test service in remote areas, it has been challenged by the lack of national guidelines, waste disposal, inventory management, and quality assurance (QA) monitoring.10

HIV self-testing, based on rapid testing methods, has allowed individuals who would otherwise refrain from testing in fear of discrimination to perform the test privately and start proper intervention. The World Health Organization (WHO) has prequalified several HIV rapid tests for HIV self-testing, including the Insti HIV-1/HIV-2 antibody tests and the Oraquick rapid HIV-1/2 antibody test.10 Nucleic acid test (NAT)

The NAT identifies HIV nucleic acid, i.e., either RNA or proviral DNA, in the blood sample. This test is based on the principles of polymerase chain reaction (PCR), nucleic acid sequence-based amplification, or ligase chain reaction.11 This test has proved to be vital in situations when an antibody against HIV is absent in serum. NAT is also performed in newborns of HIV-infected mothers. Unlike other assays, this test can detect HIV even after recent or possible exposure to the virus. Furthermore, NAT can quantify viral load.

Revolutions in Infectious Disease Testing Conclusions

The advancements in HIV diagnostic assays have played a vital role in identifying, staging, and monitoring infected individuals, even when they are under antiretroviral therapy. These assays have played an important role in surveillance and identification of transmission hot spots. Extraordinary progress in HIV testing methodologies has not only reduced false positives but decreased assessment time as well. References Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med. 2011;1(1):a006841. doi: 10.1101/cshperspect.a006841. Foster JE., et al. Viruses as Pathogens: Animal Viruses, With Emphasis on Human Viruses. Viruses. 2018; 157-187. doi.org/10.1016/B978-0-12-811257-1.00007-3 Dasgupta A, Wahed. Human immunodeficiency virus (HIV) and hepatitis testing. Clinical Chemistry, Immunology and Laboratory Quality Control (Second Edition). 2021; 513-533. doi.org/10.1016/B978-0-12-815960-6.00015-7 Konrad BP, et al. On the duration of the period between exposure to HIV and detectable infection. Epidemics. 2017; 20, 73-83. doi.org/10.1016/j.epidem.2017.03.002 Davis LE. Acute viral meningitis and encephalitis. Infections of the Nervous System, 1987; 156-176. doi.org/10.1016/B978-0-407-02293-5.50014-3 Pant PN. Oral fluid-based rapid HIV testing: issues, challenges and research directions. Expert Review of Molecular Diagnostics. 2007; 7 (4), 325-328, DOI: 10.1586/14737159.7.4.325 Abdullah DM, et al. The contemporary immunoassays for HIV diagnosis: a concise overview. Asian Biomed (Res Rev News). 2023;17(1):3-12. doi: 10.2478/abm-2023-0038. Alexander TS. Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution. Clin Vaccine Immunol. 2016;23(4):249-53. doi: 10.1128/CVI.00053-16. Aidoo S, et al. Suitability of a rapid immunochromatographic test for detection of antibodies to human immunodeficiency virus in Ghana, West Africa. J Clin Microbiol. 2001;39(7):2572-5. doi: 10.1128/JCM.39.7.2572-2575.2001. Parekh BS, et al. Diagnosis of Human Immunodeficiency Virus Infection. Clin Microbiol Rev. 2018;32(1):e00064-18. doi: 10.1128/CMR.00064-18. Garrett, P. E. Quality control for nucleic acid tests: Common ground and special issues. Journal of Clinical Virology. 2001; 20(1-2), 15-21. doi.org/10.1016/S1386-6532(00)00150-5

Further ReadingAll HIV ContentThe Economic Impacts of AIDSRecent Advancements in Treating HIV

Last Updated: Nov 29, 2024

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Politics

Nigel Farage and Rupert Lowe escalate feud with new war of words

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Nigel Farage and Rupert Lowe escalate feud with new war of words

The bitter war of words between Nigel Farage and Reform MP Rupert Lowe has dramatically escalated with the pair launching fierce new personal attacks on each other.

Mr Farage revealed accusations of bullying by Mr Lowe and accused him of falling out with all his fellow Reform UK MPs, with too many “outbursts” using “inappropriate language”.

And he took the highly unusual step of quoting a Labour minister, Mike Kane, who said after a confrontation with Mr Lowe in the Commons that his anger “showed a man not in charge of his own faculties”.

On Friday, party chairman and Farage lieutenant Zia Yusuf and chief whip Lee Anderson MP disclosed accusations that two female workers had complained of “serious bullying” in Mr Lowe’s offices, and said he had been reported to police over allegations he threatened Mr Yusuf with physical violence.

Mr Lowe, who has been suspended by the parliamentary party, denied the claims.

The worsening of the feud between the Reform UK leader and the millionaire MP for Great Yarmouth came in articles in The Sunday Telegraph in which they both furiously attacked each other.

Lowe alleges ‘witch hunt’

More on Nigel Farage

Mr Lowe stepped up his verbal onslaught on Mr Farage by claiming that a “witch hunt” against him risked destroying Reform’s attempts at removing Labour from power.

And he claimed that at a time when Reform UK’s poll ratings were rising the attacks on him by the party would be a turn-off to voters, declaring: “Infighting failed the Tories – and it’s failing Reform.”

Mr Farage also began his Telegraph article by claiming: “If the last general election taught us anything, it is that the public does not like political parties that engage in constant infighting.”

But he claimed that thanks to Mr Lowe “unloading a barrage of criticisms against our operations and its main actors”, Reform’s unity has been dented.

Rupert Lowe MP. Pic: PA
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Rupert Lowe MP. Pic: PA

‘Containment strategies invariably fail’

Mr Farage said Mr Lowe had “managed to fall out with all his parliamentary colleagues in one way or another”, adding: “We did our best to keep a lid on things but, in the end, containment strategies invariably fail.”

He then referred to a Commons clash with Mr Kane just before Christmas, after Mr Lowe staged a debate about a damaged ship containing toxic cargo docked in his Great Yarmouth constituency.

“Mr Lowe was unhappy with the answer that he received from Mr Kane and, at the end of the debate, he crossed the floor to make his feelings known,” Mr Farage wrote.

“A confrontation ensued. Heated language was heard. The minister’s shoulder was pushed. In the end, the Serjeant at Arms had to step in to calm things down between the two parliamentarians.

“Commenting on Mr Lowe’s conduct later, Mr Kane (said) ‘the anger displayed towards me clearly showed a man not in charge of his own faculties’. Nobody in Reform UK said anything publicly about what had happened. Instead, we carried on.

“Yet the fact is that, sadly, there have been too many similar outbursts from Mr Lowe, often involving the use of inappropriate language, to the despair of our chief whip, Lee Anderson.

“I have been surprised and saddened at this behaviour. Certainly, I never saw anything like it in the European Parliament in 2019 when I was the leader of the Brexit Party and Mr Lowe was an MEP colleague.”

Read more:
Lowe invites Farage to dinner
Farage gives up sole control of Reform
Party passes 200,000 members

(L-R) Nigel Farage and party chairman Zia Yusuf. Pic: PA
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(L-R) Nigel Farage and party chairman Zia Yusuf. Pic: PA

On bullying allegations, Mr Farage wrote: “Last week, the chairman of Reform UK, Zia Yusuf, showed me two letters sent by female members of staff to our party headquarters. Each letter contained an accusation of workplace bullying involving Mr Lowe.

“One of the incidents in question is alleged to have taken place within the parliamentary estate. Both women’s letters stated that these allegations had been reported to the parliamentary authorities.

“As a responsible political party, Reform UK has a duty of care to every single member of staff, whether they are employed by us directly or indirectly.

“With that in mind, I believe that our chairman was entirely right for Reform to appoint a KC to conduct an independent inquiry. It is inconceivable that we could simply ignore such allegations.”

Rupert Lowe. File pic: PA
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Pic: PA

‘I will not tolerate these falsehoods’

In his Telegraph article, Mr Lowe repeated his claim that there is no credible evidence against him and he was removed from the party before any investigation had started.

“I will not tolerate these falsehoods, and discussions have already taken place with my legal team,” he wrote. “Is it a surprise that these allegations were made public the day after I made reasonable criticisms of Nigel Farage and the Reform leadership?

“It is a witch hunt, plain for all to see. I have been entirely frozen out of the Reform machine over the last few months, in a deliberate and calculated way.”

Without naming Mr Farage, deputy leader Richard Tice or Mr Yusuf, he said the Reform UK leadership was unable even to accept the most mild constructive criticism.

Turning on Mr Yusuf, he wrote: “The allegations against me from the chairman relate to an incident in December, but he only reported them to the police the day after my reasonable questioning was published.

“Take from that what you will. I don’t feel sorry for myself. I feel sorry for the millions of decent British men and women who put their faith in Reform. They deserve better than this vicious charade.”

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And warning of the damage the feuding was causing, Mr Lowe said: “Everything has been put at risk. Everything. The future of the Right in Britain is now in peril. How can Reform claim to be a party awaiting government when they can’t even follow basic process?

“Reform has been rising in the polls for months. But this spectre of infighting will leave the party looking unserious and turn voters off. Infighting failed the Tories – and it’s failing Reform.”

But Mr Lowe concluded with an olive branch. “On multiple occasions, I have invited Nigel Farage for dinner over the last few months,” he revealed. “Every single one has been refused or ignored.

“Again, I offer a public invitation to Nigel. Let’s have dinner and resolve this in the matter that our members, supporters and country would expect. Any time, any place.”

He added: “I want Reform to be professional, to be fair, to be serious. We must offer a credible alternative to the uniparty that has so failed so spectacularly.

“The leadership’s behaviour this week has undermined that cause, not only in the eyes of the electorate, but also in those of serious individuals across business and industry that any party of government needs to win over.”

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Politics

Negotiators appeal to man to come down from Big Ben clock tower

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Negotiators appeal to man to come down from Big Ben clock tower

Negotiators at Westminster have been trying to persuade a man to come down after he scaled the clock tower which houses Big Ben.

The barefoot man has been spoken to by emergency crews and negotiators a number of times during the day but he remains several metres up the Elizabeth Tower on a ledge where he is holding a Palestinian flag in an apparent protest.

The Metropolitan Police said they were called to the scene in central London at 7.24am on Saturday.

Photographs have shown the man sat on the ledge with the flag and a keffiyeh, a headdress worn by men in the Middle East, wrapped around the decorative stonework on the tower.

A large red stain which appears to be blood can be seen on the side of the tower around the climber’s feet.

The bare-footed protester is holding a Palestinian flag. Pic: PA
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The barefoot man is holding a Palestinian flag. Pic: PA

Following the security breach at Parliament, a fire engine later raised an aerial ladder platform to the same height as the man’s position.

Three people standing on the platform have been talking to the man, who is several feet away.

Climber shares videos on social media

The climber has been sharing videos on Instagram from his viewpoint on the tower.

He tells negotiators he will come down “on his own terms”.

In the footage, negotiators appear to raise concerns about an injury to his foot, saying there is “quite a lot of blood” and that his clothes are not warm enough as temperatures drop after sunset.

But the man insists he is safe and says: “I will come down on my own terms, I have said this. But right now I am saying I am safe.

“If you come towards me you are putting me in danger and I will climb higher.”

Also in a video, a woman in plain clothes says: “At some point you have to come down. How long do you think you are going to be there? How long do you think you are able to be there?”

Her voice is then barely audible as she appears to say “your message was to say ‘Free Palestine'” before she encourages him to come down.

In one of the other videos, the man seems to suggest he plans to stay on the ledge for three and a half days.

X
Image:
People in a cherry picker talk to the man

The whole of Westminster Bridge was closed later in the morning as emergency services responded to the incident.

And parliamentary tours on Saturday were cancelled.

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‘Unbelievable he’s up there’

A Metropolitan Police spokesperson said: “Officers are at the scene working to bring the incident to a safe conclusion. They are being assisted by the London Fire Brigade and the London Ambulance Service.”

Bridge Street, which is at the north end of Westminster Bridge, has been closed to allow emergency services to deal with the incident.

Pic: AP
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Pic: AP

The man who has climbed up Big Ben this morning
Image:
The man before the cherry picker was raised

Pic: PA
Image:
Pic: PA

At least nine emergency service vehicles have lined the street in central London as crowds look on from beyond a police cordon.

A parliamentary spokesperson said: “We are aware of an incident on the Parliamentary Estate this morning, which is being handled by the Metropolitan Police, assisted by the London Fire Brigade and the London Ambulance Service.

“Parliament takes security extremely seriously, however we do not comment on the specifics of our security measures or mitigations. As a result of this incident, tours of the Parliamentary Estate today have unfortunately had to be cancelled.”

It comes as dozens of people gathered for a pro-Palestinian protest in London.

The crowd assembled on the corner of Parliament Square and appeared to be showing support for the man who climbed up Big Ben.

Trump’s Turnberry golf course vandalised

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‘Gaza not for sale’ on Trump golf course

The protest in Westminster comes as the Palestine Action group said it had sprayed “Gaza is not for sale” on Donald Trump’s Turnberry golf course in Scotland.

Sharing an image of the vandalism on Saturday morning, the group wrote on X: “Whilst Trump attempts to treat Gaza as his own property, he should know his own property is within reach.”

The Turnberry protest comes after the American president claimed the US will “take over the Gaza Strip and we will do a job with it too”.

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Environment

Meet the newest EV from Hyundai – new HX19e electric excavator

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Meet the newest EV from Hyundai – new HX19e electric excavator

The HD arm of Hyundai has just released the first official images of the new, battery-electric HX19e mini excavator – the first ever production electric excavator from the global South Korean manufacturer.

The HX19e will be the first all-electric asset to enter series production at Hyundai Construction Equipment, with manufacturing set to begin this April.

The new HX19e will be offered with either a 32 kWh or 40 kWh li-ion battery pack – which, according to Hyundai, is nearly double the capacity offered by its nearest competitor (pretty sure that’s not correct –Ed.). The 40kWh battery allows for up to 6 hours and 40 minutes of continuous operation between charges, with a break time top-up on delivering full shift usability.

Those batteries send power to a 13 kW (17.5 hp) electric motor that drives an open-center hydraulic system. Hyundai claims the system delivers job site performance that is at least equal to, if not better than, that of its diesel-powered HX19A mini excavator.

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To that end, the Hyundai XH19e offers the same 16 kN bucket breakout force and a slightly higher 9.4 kN (just over 2100 lb-ft) dipper arm breakout force. The maximum digging depth is 7.6 feet, and the maximum digging reach is 12.9 feet. Hyundai will offer the new electric excavator with just four selectable options:

  • enclosed cab vs. open canopy
  • 32 or 40 kWh battery capacity

All HX19es will ship with a high standard specification that includes safety valves on the main boom, dipper arm, and dozer blade hydraulic cylinders, as well as two-way auxiliary hydraulic piping allows the machine to be used with a range of commercially available implements. The hydraulics needed to operate a quick coupler, LED booms lights, rotating beacons, an MP3 radio with USB connectivity, and an operator’s seat with mechanical suspension are also standard.

Like its counterparts at Volvo CE, the new Hyundai excavator uses automotive-style charging ports to take advantage of existing infrastructure at fleet depots and public charging stations. More detailed specifications, dimensions, and pricing should be announced by bauma.

Electrek’s Take

HX19e electric mini excavator; via Hyundai Construction Equipment.

The ability to operate indoors, underground, or in environments like zoos and hospitals were keeping noise levels down is of critical importance to the success of an operation makes electric equipment assets like these coming from Hyundai a must-have for fleet operators and construction crews that hope to remain competitive in the face of ever-increasing noise regulations. The fact that these are cleaner, safer, and cheaper to operate is just icing on that cake.

SOURCE | IMAGES: HD Hyundai; via Construction Index, Equipment World.

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